Temperature-controlled fluid manifold for a fluid manifold for a fluid system of an automated sample analyzer

ABSTRACT

Temperature-controlled fluid manifold for a fluid system of an automated sample analyzer of the type for analyzing a series of liquid samples flowing seriatum to quantitative analysis for a constituent of interest. The basic elements of the temperaturecontrolled manifold may be permanently combined with a wide variety of other components to meet the requirements of many different chemistries to provide many different temperaturecontrolled manifolds each suited for analysis of a different constituent of a sample such as blood for example. In each particular manifold, the sample may be treated as by combination and mixing with any appropriate reagent or reagents under temperature-controlled conditions for subsequent analysis as in a colorimeter for example. The manifold may be significantly smaller in size and less costly than conventional manifolds. The aforementioned basic manifold elements comprise a thermally conductive plate or block heated by conduction from a temperature-controlled source of heat, which plate has an outer, exposed surface of substantial area, and an appropriate number of appropriately configured fluid passageway portions, such as helical mixing or helical time-delay paths, encapsulated in a solid material characterized by a heat storage capacity and which material is supported in an appropriate location on the lastmentioned surface for thermal transfer by conduction to the material from the plate. The manifold includes a cover effectively tending to stagnate the ambient atmosphere around such encapsulated fluid passageway portions.

- United sate Patent 11 91- Diebler a a1,

Primary ExaminerR. E. Serwin Attorney, Agent, Rockwell Int. Cl.

TEMPERATURE CONTRQLLED FLUID MANIFOLDFQR A FLUID-SYSTEM OF AN 7 AUTOMATED SAMPLE ANALYZER Inventors: Herman G, piehler, North Haledon;

Steven Andrew Gyori; Allendale;

William J. C. McCandless, Ringwood, all of NJ. V v

Technicon Instruments Corporation, Tarrytown,

Filed; June 7, 1972 Appl. No.: 260,551

Assignee;

us. or. 23/259, 23/253 R, 165/18 rider Search ,2 3/230. 253, 292, 259; 5 126/263; 137/334; 165/18 References Cited UNITED STATES PATENTS 1/1964 Ferrari, Jr.; 23/253 X 9/1966 Williams et al. 23/253 Smythe et al.-.... 23/253 X Waters..... 12/1970 Smythe etal. 9/1971 'Mclntyre;.. 9/1972 Ferrari 10/ l972= I 10/1972 25/253 x 23/253 x 23/253 x .23/2'59 x 23/253 x or Firm- -S. P. Tedesco; s. E.

'bie'nt atmosphere [57] ABSTRACT Temperature-controlled fluid manifold for a fluid system of an automated sample analyzer of the type for analyzing a series of liquid samples flowing seriatum to quantitative analysis for a constituent of interest. The

basic elements of the temperature-controlled manifold may be permanently combined with a wide variety of other components to meet the requirements of many different chemistries to provide many different temperature-controlled manifolds each suited for analysis of a different constituent of a sample such as 1 blood for example. In each particular manifold, the

sample may be treated asby combinationand mixing with any appropriate reagent or reagents under temperature-controlled conditions for subsequent analysis as in a colorimeter for example. The manifold may be significantlysmaller in size and less costly than conventional manifolds. The aforementioned basic manifold elements comprise a thermally conductive plate or block heated by conduction from a temperature-controlled source of heat, which plate has an outer, exposed surface of substantial area, and an appropriate number of appropriately, configured fluidv passagewayportions, suchas helical mixing or helical time-delaypaths; encapsulated in a solid material characterized by a heat storage capacity and. which materialti's supported in an appropriate location on the lastmentioned surface for thermal transfer by conduction to the material fromthe plate. 'The'mani'fold includes a-cover effectively tending'to stagnate the amaround= such-encapsulated fluid passagewayportions.

10 Claims, Drawing Figures 51 May 21,1974

PATENTEDIAYZI m4 sum 2 w 2 om N TEMPERATURECONTROLLED FLUID MANIFOLD FOR A FLUID SYSTEM OF AN AUTOMATED SAMPLE ANALYZER BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a temperature-controlled fluid manifold for a fluid system of an automated sample analyzer of the type for analyzing a series of liquid samples flowing seriatum to quantitative analysis for a constituent of interest.

2. Prior Art Apparatus for the continuous analysis of fluids are well known. Such an apparatus is disclosed in Skeggs U.S. Pat. No. 2,797,149 issued June 25, 1957. Skeggs U.S. Pat. No. 2,879,141 issued Mar. 24, 1959 discloses analysis apparatus of an automated type in which samples are fed in a flowing stream by means of a takeoff device which aspirates liquid from each of a plurality of sample containers which are sequentially presented thereto by a sampler assembly. Such apparatus is commonly employed for the analysis of various fluids. Skeggs etv a1. U.S. Pat. No. 3,241,432 issued Mar. 22, 1966 discloses automated apparatus for performing multiple quantitative analyses on different portions of a single sample of a series of such samples, each analysis being for adifferent specific sample constituent. As shown and described in the last-mentioned patent by way of example, such automated analysis apparatus may include for analysis purposes a'series of different analytical manifolds for different tests, the flow from each one of which is to analysis by a colorimeter or a spectral flame photometer for analysis of different portions of a same sample. However, other conventional photometric analysis devices or ion-selective electrodes, for example, may be used foranalysis purposes in similar automated sample analysis apparatus.

The aforementioned Skeggs U.S. Pat. No. 2,797,149 which discloses an automated analyzer which is essentially a one-channel or a one-manifold system, and in the system illustrated in FIG. 3 of the drawings there is a water bath, indicated at 64, to control the temperature of a treated sample portion flowing through the bath in a helical coil. The water in the water bath 64.is heated by an immersion heater of the rod type, and the temperature of the water bath 64 is suitably regulated. The water bath 64 is of considerable size and may be supported on a table surface. It is also relatively expensive. Another similar water bath, indicated at 99, is shown in a different system described in that patent and illustrated in FIG. 4. Aforementioned Skeggs US. Pat. No. 2,879,141 discloses in FIG. 8 of the drawings similar fluid baths for the temperature control of a treated sample portion flowing therethrough.

Aforementioned Skeggs et a1. U.S. Pat. No. 3,241,432 discloses as in FIG. l of the drawings heating baths 141 and 142 associated with respective ones of a pair of different analytical manifolds to conduct different tests on different portions of a same sample which is one of a series of such samples. The heating bath contains oil which is heated as by a heater for heating the oil in each instance and the treated sample portion is flowed through the respective bath in a helical passageway which is encapsulated by the oil. The last-mentioned heating baths are relatively large and costly though they may be smaller and less costly than the heating baths described above with reference to the other aformentioned Skeggs patents.

A disadvantage of the aforementioned heating baths of the prior art aside from possible heating fluid leakage, resides in the fact that, at best, it would be difficult to miniaturize such baths to the size desirable for use in todays automated sample analyzer wherein more tests are performed on a single sample, that is where the sample of a series undergoing analysis is divided into many more aliquots, each of which receives a different test in a different manifold for a constituent of interest in each sample. Even if possible to miniaturize such conventional heating baths as described above to desirable dimensional ranges for dimensionally small manifolds, such water or oil bath heaters would be relatively costly. Furthermore, plural heating baths have had individual temperature-control elements, one for each heating bath. It has been found in the use of such plural heating baths that there is a lack of temperature uniformity between such heating baths.

SUMMARY OF THE INVENTION One object of the invention is to provide an improved temperature-controlled fluid manifold for a fluid system of an automated sample analyzer of the type for analyzing a series of liquid samples flowing seriatum to quantitative analysis for a constituent of interest. Anotherobject is to provide in such temperaturecontrolled manifold, basic elements of the manifold which may be permanently combined with a wide variety of other components to meet the requirements of many different chemistries to provide many different temperature-controlled manifolds each suited for analysis of a different constituent of the sample such as blood for example. Still another object is to provide, in such a manifold, for treatment of the respective sample portion as by combination and mixing with any appropriate reagent or reagents under temperaturecontrolled conditions for subsequent analysis as in a colorimeter for example.

Another object is to provide a manifold having plural temperature-controlled fluid passage portions all under the control of a single temperature regulator, effecting better uniformity of temperature-control to the extent that thetemperature of one such fluid passage portion effectively tends to .be the sameas the temperature of the other such fluid passageway portions.

Still another object is to provide a manifold which may be significantly smaller in size and less costly than conventional manifolds, and which is very durable and less subject to breakage of parts than conventional manifolds.

There is provided a manifold, such as characterized above, the basic elements of which comprise a thermally conductive plate or block heated by conduction from a temperature-controlled source of heat, which plate has an outer, exposed surface of substantial area, and an appropriate number of appropriately configured fluid passageway portions, such as helical mixing or helical time-delay coils, encapsulated in a solid material characterized by a heat storage capacity and which material is supported in a selected one of a plurality of available locations on the last-mentioned surface for thermal transfer by conduction to the material from the plate. The manifold includes a cover effectively tending to stagnate the ambient atmosphere around such encapsulated fluid passageway portions.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:

FIG. 1 is a front elevational view of a temperaturecontrolled fluid manifold, with the cover removed, embodying the invention;

FIG. 2 is a bottom view of the manifold of FIG. 1; and

FIG. 3 is a sectional view taken along line 33 of FIG. 1.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS With reference to the drawings, particularly FIGS. 2 and 3 thereof, the manifold is shown as comprising an oblong base preferably constructed of material having thermal insulating properties, which may be of a plastic material. The base 10 has a longitudinal, horizontally extending opening therethrough. As shown in FIGS. 1 and 2 the outer part of the base 10 is cut-away in part as at 12 to receive a heater block or plate 14 having an outer, exposed surface 16 of substantial area and which is substantially flush with the right-hand end portion of the base 10 as viewed in FIG. 1.

Secured to the underside of the block or plate 14 in the location indicated in FIGS. 1 and 2 is a thermostatically controlled heater element 18 preferably in direct contact with the last-mentioned side of the plate 14 for the transfer to the latter of thermal energy from the heater element 18. The heater element 18 is preferably of the electrical type, and is located within the aforementioned horizontally extending opening through the base 10. The heater plate 14 is characterized, at least to some extent, in that the material from which it is formed has good thermal conductivity characteristics. The material of the plate 14 is preferably a metal and may be formed of powered aluminum or stainless steel, for example.

In a vertical plane intermediate the plate 14 and the inner extremity of the base 10 the base may be provided with an upwardly directed shoulder 20 to act as a stop and an abutment for the manifold cover 22 to limit inward movement of the last-mentioned cover with reference to the base 10. The rigid cover 22 snugly fits over the base 10 and if desired may be removed from the manifold on outward sliding movement of the cover 22. It is to be understood that the cover may be supported from the manifold in any suitable manner as by being hinged thereto (not shown) and any suitable stop may be employed to limit closing movement of the cover 22. The cover is preferably transparent so that, when the cover is assembled with the manifold base, a user may view through the cover at least certain fluid stream portions in the use of the manifold, as will appear more fully-hereinafter.

As best shown in FIG. 1 one or more temperaturecontrolled fluid passageway portions are associated with the heater plate 14 outside the plate 14, two such temperature-controlled portions being illustrated by way of example and indicated at 24 and 26.

Each such temperature-controlled fluid passageway portion 24, 26 defines a fluid passageway therethrough which is encapsulated in a solid material having heat conductive and storage characteristics which material may be formed of a metal such as lead-or aluminum for example. The passageway portion 24 is formed as a helix from end-to-end with an inlet at one end thereof extending through an encapsulation material and an outlet at the other end thereof, also extending through the encapsulation material as shown in FIG. 1.

The temperature-controlled fluid passageway portion 26 includes two helical portions in axial arrangement with reference to one another and with communication therebetween, that is between the outlet of the first helical portion and the inlet of the second helical portion. The inlet of the firstmentioned helical portion of the fluid passageway portion 26 extends through the encapsulation material as shown in the last-mentioned view and the outlet of the second mentioned helical portion of the fluid passageway portions 26 extends through the encapsulation material as also shown in this view.

It has been found advantageous to form the aforementioned fluid passageway portions 24 and 26 in a glass material and then encapsulate the glass material in the aforementioned heat storage material. One of the reasons for this is that glass of certain well-known types is very inert and not subject to corrosive attack. From the foregoing it will be understood that it is not usually desirable to form the fluid passageway portion 24 and 26 directly in the encapsulating material having heat storage properties. The encapsulating material is in intimate contact with the glass material, completely surrounding the helical portions of the glass. In addition, the encapsulation material fills the axial area (FIG. 3) around which the turns of glass coil are formed. It has been found that if the encapsulation material used is lead, a temperature-controlled fluid passageway portion such as the portion 24 may be encapsulated by molding the prefonned glass helix of the portion 24 within the heat storage material. Of couse in such a molding operation access must be provided to the inlet and the outlet of the portion 24.

The encapsulated fluid passageway portions 24 and 26 are secured to the outer surface 16 of the heater plate 14 in any suitable manner as by cementing the units to the plate 14 in the desired location on the outer surface 16 of the heater plate. The manner of securing the encapsulated temperaturecontrolled fluid portions 24 and 26 to the heater plate surface 16 is not deemed critical, but it should be understood that the units 24 and 26 must be in proximity to the surface 16 of the heater plate to receive thermal conduction therefrom. It will also be noted in FIG. 1 that the electrical heater element 18 is preferably located substantially centrally of the area occupied by the units 24, 26 in plane laterally inwardly of the plane of the heater plate 14, for substantially uniform heat distribution of both units 24, 26.

The number and configuration of the temperaturecontrolled fluid passageway portions will depend upon the particular chemical and other requirements of the particular intended use of the manifold. The illustrated manifold is for the quantitative determination of SGPT in a blood sample. Accordingly the fluid connections to the manifold and any temperature-controlled fluid passageway portions must be suitable to the particular test. As seen in the lower lefthand corner of FIG. 1 there is provided a fitting 28 which may be of glass and constructed in accordance with the technique of fabrication illustrated and described in the co-pending US Pat. application of De Angelis et al., Ser. No. 246,966 filed on Apr. 24, 1972, now US. Pat. No. 3,770,405. This fitting 28 does not require detailed explanation here. It is sufficient for present purposes that the fitting 28, which is suitably secured to the surface 16 of the heater plate, has a passageway formed therein in communication with flexible tubes 30, 32, 34 all of which are inlets into the internal passageway in the fitting 28. The last-mentioned passageway has an outlet in communication with the inlet of glass tube 36. The material of which these tubes are formed is not critical but for the sake of convenience they may be flexible and formed of a suitable inert material. Tube 36 has an outlet coupled to the inlet of temperature-controlled unit 26. Downstream a short distance from the lastmentioned inlet, another inlet in temperaturecontrolled unit 26 is provided in communication with the outlet of tube 38 which may be formed of inert glass and which is for the purpose of introducing another fluid into the temperature-control unit 26.

Miscible fluids flowing into the temperature-control unit 26 through the tubes 36 and 38 are mixed within the first section of the double helix of the unit 26. Prior to the introduction of fluid from the last-mentioned section of the double helix to the second section of the double helix of unit 26, another miscible fluid is added to the temperature control unit 26 through a plastic tube 40 having an outlet coupled to a port in the section of the temperature-control unit 26 providing communicationbetweenthe two helical sections thereof, so that the combined-stream ispassed through the second or right-hand helical portion-of the unit 26'for mixing of the miscible fluid therein.-

The fluid flowing into the inlet of tube 32 is immiscible with the liquid flowinginto the inlet of tube 30 and such immiscible fluid may be an inert gas which segments the stream flowing from the outlet of tube 30 in the aforementioned passage in fitting 28. Another liquid immiscible with the liquid inletted from the tube 30 is inletted from the tube34 into the last-mentioned passage in the fitting 28 to combine with a stream in the fitting 28. The segmented liquid stream outletted from the fitting 28 to the tube 36 is combined with the sample inletted into the stream through the outlet of tube 38. The sample flowing into tube 38 is itself in segmented condition while flowing in the tube 38. The inlets of the tubes 30, 32, 34, 38 and 40 are not shown but it is to be understood that they may be some distance away from the manifold and haveany type of suitable connection to the sources-of the respective fluids, for flow through the manifold induced in a conventional manner by a pressure differential. As indicated in FIGS. 1 and 2, the tubes 34 and 40 enter the manifold by passing through respective holes in the base beyond the right-hand extremity of the heater plate 14 as seen in FIG. 1.

The tubes 30, 32 and 38 may enter the-manifold through a common opening 42 (F IG. 2) inthe cover 22 which opening is sufficiently small to essentially create a stagnant ambient atmosphere within the cover 22 so that the temperature-controlled units 24 and 26 are not subject to drafts when the cover 22 is in place, and changes in the temperature of the ambient atmosphere within the cover 22 are effectively inhibited when room temperature changes.

As previously indicated, all temperaturercontrolled fluid passageway portions are under the common control of a single heat regulator, and there is a large degree of uniformity of the temperature of one temperature-controlled fluid passageway portion with the temperature of all the other such fluid passageway portions. The temperature may be in the order of 37C.

While the temperature-controlled fluid passageway portions 24 and 26 illustrated and described herein are of the type wherein a sample is treated as by mixing or passing through an incubator, fluid temperaturecontrolled passageway portions of other types and within the purview of the invention may be utilized such as a non-illustrated temperature-controlled flow controller for a reagent fluid, associated in a similar manner with the heated plate 14, which flow controller may be secured to the face of the plate 14 obverse to that on which the temperature-controlled fluid passageway portions 24 and 26 are secured.

The manifold may be mounted in the attitude of F 1G. 1 on a panel of which a large number of other manifolds are also mounted in an analytical chemistry module of an automated fluid sample analyzer.

The flow from the exit of the temperature-controlled unit 26 is through glass tube 44 having an inlet end coupled to the fluid outlet end of the temperaturecontrolled unit 26 and having an outlet end coupled to an inlet conduit 46 in a flow cell 48. The flow cell 48 may be of any conventional construction and is secured in a conventional manner to the heater plate 14 though it may be spaced outwardly from the surface 16 thereof. The flow cell 48 has a fluid passageway portion 50 to one end of which the outlet of the inlet 46 is connected, which portion 50'is arranged longitudinally of an optical path. The fluid outlet from the portion 50 is to the flow cell outlet 52. Beyond the inlet 46 and the outlet 52 and within the passage portion 50, there are provided transparent fluid seals, not shown, which lie in the optical path. 7

Optical fiber assemblies 54, 56 of elongated form and of conventional construction each have an end aligned and supported with reference to the respective ends of fluid passageway 50, lying within the optical path, and which ends of the assemblies 54 and 56 are disposed outwardly of the respective last-mentioned fluid seals of the passage 50. The optical fiber assembly 54 enters the manifold through an opening (not shown) in the base 10 and passes with clearance through the heater plate 14. The optical fiber assembly 56 exits from the manifold through the base 10 and is likewise'provided with clearance with the heater plate 14.

Utilizing the optical fiber assemblies 54 and 56, the stream in the passageway 50 of the flow cell 48 is analyzed colorimetrically at a location remote from themanifold, and the signal from the colorimeter (not shown) is suitably processed and may be displayed in typical, non-illustrated fashion.

The outlet 52 of the flow cell 48 is coupled to the inlet end of a glass tube 58 for the flow through the tube 58 of the stream exiting from flow cell 48. The outlet end of the tube 58 is'coupled to the inlet end of temperature-controlled fluid passageway unit 24 and the stream flowing through the helix of the illustrated unit 24 under temperature-controlled conditions is incubated therein.

A glass tube 60 has an inlet end coupled to the fluid 64 and 66 are utilized in a colorimetric analysis of the fluid stream passing through the flow cell 62 in a similar manner. While the fluid outlet of the flow cell 62 is shown as coupled to the inlet end of a plastic waste tube 68 exiting from the manifold through a hole, not shown, in the base 10 (FIGS. 1 and 2) for simplicity of illustration of the invention, in practice the flow from the flow cell 62 is directed through another temperature-controlled unit (not shown) similar to the unit 24 and is subsequently passed to still another flow cell (not shown), and it is from the last-mentioned flow cell that the stream flows to waste through the manifold in the manner of the exit tube 68 passing through the base 10. it is to be understood that the non-illustrated additional temperature-controlled fluid passage and the nonillustrated flow cell which receives the stream therefrom are supported on the heater plate 14 in similar fashion and are similarly configured.

The illustrated manifold may be approximately 12% inches long and 2 /2 inches wide and may take the form of a cartridge suitably secured through the base 10 to a vertical panel of a multiple analyzer on which-panel a relatively large number of such cartridges for different chemistries or analyses may be mounted in close proximity to one another. It will be understood that the manifold of the invention may utilize other analysis means than those illustrated. For example, the analysis may be by potentiometric measurement.

While the invention has been illustrated with reference to a preferred form and several embodiments have been discussed, it will be apparent, especially to those versed in the art, that the invention may take other forms and is susceptible of various changes in details without departing from the principles of the invention.

What is claimed is:

1. In a manifold for an automated fluid analyzer, having at least one temperature-controlled fluid passageway portion, the combination of: a support, a heated plate, having thermal transfer characteristics, supported on such support and having an exposed outer surface area, and a fluid passageway portion encapsulated in a block of solid material having thermal storage characteristics, providing access to an inlet and an outlet in said passageway portion, and located in a selected one of a plurality of locations on said surface area, said block of encapsulation material having a substantial surface area opposed to and secured in close proximity to said heated plate for thermal transfer by conduction from said plate to said block of material, means to regulate the heating of said plate, and a cover extending with clearance over said block encapsulating said fluid passageway portion, effectively tending to stagnate the ambient atmosphere about the external exposed surface of said block of encapsulation material, thereby tending to prevent thermal dissipation from the lastmentioned surface.

2. A manifold as defined in claim 1, wherein: a plurality of different ones of such encapsulated fluid passageway portions are secured to and in close proximity to said heated plate for thermal transfer thereto from said plate.

3. A manifold as defined in claim 1, wherein: said fluid passageway portion is of spiral configuration.

4. A manifold as defined in claim 1, wherein: said fluid passageway portion is of generally duplex spiral configuration with a fluid admission port for the admixture of a fluid to the spiral passageway between the two parts thereof.

5. A manifold as defined in claim 1, further including a fluid analyzer supported from said support and in fluid flow communication with said passageway portion.

6. A manifold as defined in claim 1, further including at least two fluid analyzers supported from said support in fluid communication with each other and with said fluid passageway portion.

7. A manifold as defined in claim- 1, wherein: said cover extends over the entire manifold.

8. A manifold as defined in claim 1, further including heating means for heating by conduction said heater plate.

9. A manifold as defined in claim 1, wherein: said fluid passageway portion is formed of an inert material and the last-mentioned material is encapsulated in said block.

10. A manifold is defined in claim 2, wherein: the manifold has a plurality of fluid inlet and outlet conduits external thereto and extending within said cover. 1 

2. A manifold as defined in claim 1, wherein: a plurality of different ones of such encapsulated fluid passageway portions are secured to and in close proximity to said heated plate for thermal transfer thereto from said plate.
 3. A manifold as defined in claim 1, wherein: said fluid passageway portion is of spiral configuration.
 4. A manifold as defined in claim 1, wherein: said fluid passageway portion is of generally duplex spiral configuration with a fluid admission port for the admixture of a fluid to the spiral passageway between the two parts thereof.
 5. A manifold as defined in claim 1, further including a fluid analyzer supported from said support and in fluid flow communication with said passageway portion.
 6. A manifold as defined in claim 1, further including at least two fluid analyzers supported from said support in fluid communication with each other and with said fluid passageway portion.
 7. A manifold as defined in claim 1, wherein: said cover extends over the entire manifold.
 8. A manifold as defined in claim 1, further including heating means for heating by conduction said heater plate.
 9. A manifold as defined in claim 1, wherein: said fluid passageway portion is formed of an inert material and the last-mentioned material is encapsulated in said block.
 10. A manifold is defined in claim 2, wherein: the manifold has a plurality of fluid inlet and outlet conduits external thereto and extending within said cover. 